Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: Evidence for a neurolymphocrine system

Daniel Philip Poole, Mike Lee, Patrick Tso, Nigel William Bunnett, Sek Jin Yo, Tina Marie Lieu, Amy Shiu, Jen-Chywan Wang, Daniel Nomura, Gregory W Aponte

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a neurolymphocrine system.
Original languageEnglish
Pages (from-to)G686 - G698
Number of pages13
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume306
Issue number8
DOIs
Publication statusPublished - 2014

Cite this

Poole, Daniel Philip ; Lee, Mike ; Tso, Patrick ; Bunnett, Nigel William ; Yo, Sek Jin ; Lieu, Tina Marie ; Shiu, Amy ; Wang, Jen-Chywan ; Nomura, Daniel ; Aponte, Gregory W. / Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: Evidence for a neurolymphocrine system. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2014 ; Vol. 306, No. 8. pp. G686 - G698.
@article{31d88982d1aa4fdeb596f505d27043a0,
title = "Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: Evidence for a neurolymphocrine system",
abstract = "Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a neurolymphocrine system.",
author = "Poole, {Daniel Philip} and Mike Lee and Patrick Tso and Bunnett, {Nigel William} and Yo, {Sek Jin} and Lieu, {Tina Marie} and Amy Shiu and Jen-Chywan Wang and Daniel Nomura and Aponte, {Gregory W}",
year = "2014",
doi = "10.1152/ajpgi.00433.2013",
language = "English",
volume = "306",
pages = "G686 -- G698",
journal = "American Journal of Physiology - Gastrointestinal and Liver Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "8",

}

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: Evidence for a neurolymphocrine system. / Poole, Daniel Philip; Lee, Mike; Tso, Patrick; Bunnett, Nigel William; Yo, Sek Jin; Lieu, Tina Marie; Shiu, Amy; Wang, Jen-Chywan; Nomura, Daniel; Aponte, Gregory W.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 306, No. 8, 2014, p. G686 - G698.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: Evidence for a neurolymphocrine system

AU - Poole, Daniel Philip

AU - Lee, Mike

AU - Tso, Patrick

AU - Bunnett, Nigel William

AU - Yo, Sek Jin

AU - Lieu, Tina Marie

AU - Shiu, Amy

AU - Wang, Jen-Chywan

AU - Nomura, Daniel

AU - Aponte, Gregory W

PY - 2014

Y1 - 2014

N2 - Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a neurolymphocrine system.

AB - Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a neurolymphocrine system.

UR - http://ajpgi.physiology.org/content/ajpgi/306/8/G686.full.pdf

U2 - 10.1152/ajpgi.00433.2013

DO - 10.1152/ajpgi.00433.2013

M3 - Article

VL - 306

SP - G686 - G698

JO - American Journal of Physiology - Gastrointestinal and Liver Physiology

JF - American Journal of Physiology - Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 8

ER -